Inhibition of Efferocytosis by Extracellular CIRP-Induced Neutrophil Extracellular Traps.

ABSTRACT: Phagocytic clearance of apoptotic cells by the macrophages (efferocytosis) is impaired in sepsis, but its mechanism is poorly understood. Extracellular cold-inducible RNA-binding protein (eCIRP) is a novel damage-associated molecular pattern that fuels inflammation. We identify that eCIRP-induced neutrophil extracellular traps (NETs) impair efferocytosis through a novel mechanism. Coculture of macrophages and apoptotic thymocytes in the presence of recombinant murine CIRP (rmCIRP)-induced NETs significantly inhibited efferocytosis. Efferocytosis was significantly inhibited in the presence of rmCIRP-treated wild-type (WT), but not PAD4^-/- neutrophils. Efferocytosis in the peritoneal cavity of rmCIRP-injected PAD4^-/- mice was higher than WT mice. Milk fat globule-EGF-fa

SUBMITTER: Chen K 

PROVIDER: S-EPMC7854515 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature